The proposed study is designed to elucidate the interrelationships between cardiac lymph and acute myocardial infarction. To this end, we plan 1) to investigate various physiologic, pharmacologic, and pathologic mechanisms that may influence the volume and composition of cardiac lymph and 2) to determine the effects of such alterations in lymph on the subsequent changes that occur in the histologic, biochemical and electrical characteristics of the ischemic heart. Our pilot studies indicate that acute myocardial ischemia produces significant changes in the cardiac lymph, which presumably reflect alterations in the interstitial fluid. These changes include alterations in lactate, lysosomal sodium-potassium balance, and pH. Furthermore, our data suggest strongly that these changes play a part in the development of electrical instability and aggravate the hypoxic changes in the ischemic heart. Experiments to be carried out in dogs will be divided into four groups. In the first group, we will define the changes produced in cardiac lymph by uncomplicated, acute myocardial ischemia, and by acute ischemia associated with heart failure or shock. We will also study the effects of various proposed therapeutic agents on the composition of cardiac lymph under these circumstances. In the second group, we will investigate the effects of lymphatic drainage on the ventricular fibrillation threshold. In the third group, we will study the effects of chronic congestive heart failure on the acute ischemic process, and in the fourth group, we will investigate, in the setting of chronic congestive heart failure, the effects of draining the cardiac lymph against varying levels of outflow resistance. On the basis of our preliminary investigations, it seems warranted to suggest that further in-depth studies of the interrelationships between acute myocardial ischemia and cardiac lymph will prove fruitful and will provide a new approach to a better understanding of the pathophysiology of myocardial infarction.